Synthesis, analgesic and antipyretic activity of 2-(antipyrin-4-yl)hydrazones of 1,2,3-triketones and their derivatives

Abstract

1,2,3-Triketone 2-(antipyrin-4-yl)hydrazones were synthesized via the azo-coupling reactions of 1,3-diketones with 2-(antipyrin-4-yl)diazonium chloride. The fluoroalkyl-containing hetarylhydrazone enters into cyclocondensation with hydrazines at the 1,3-dicarbonyl fragment to yield 3-tetrafluoroethyl derivatives of pyrazole. It was found that 1,2,3-triketone 2-(antipyrin-4-yl)hydrazones and N-(2-hydroxyethyl)-substituted pyrazole exhibit analgesic activity comparable with that of their structural analog analgin (metamizole sodium), but do not possess antipyretic properties. In contrast, N-phenyl-substituted pyrazole did not exhibit analgesic properties but produced a certain antipyretic effect four hours after pyrogenic administration. Fluoroalkyl-containing compounds are less toxic substances than nonfluorinated 2-(antipyrin-4-yl)hydrazone and analgin.As is known, the widely used analgesic and antipyretic drugs are rather toxic substances [1]. We attempted to modify the antipyrine structure so as to obtain new low-toxicity compounds possessing analgesic and antipyretic properties.Using the azo-coupling reactions of 1,3-diketones (Ia and Ib) with 2-(antipyrin-4-yl)diazonium chloride (II) in the presence of sodium acetate, we obtained the corresponding 1,2,3-triketone 2-(antipyrin-4-yl)hydrazones (IIIa and IIIb). The proposed structures of these products were confirmed by the data of elemental analyses and the results of IR and 1 H NMR spectroscopic measurements. Indeed, the presence of characteristic absorption bands due to carbonyl groups (at 1660 -1680 cm -1 ) and a weak band due to the stretching vibrations of amino groups of the hydrazone fragment (at 3300 -3470 cm -1 ) in the IR spectra, as well as the absence of signals from methane protons in the 1 H NMR spectra, showed evidence for a hydrazone-diketone tautomer structure of the synthesized compounds.

Chemistry of Phosphorus Ylides: Part 41 Synthesis of Antimicrobial Agents from the Reaction of Aminoantipyrine, Coumarin- and Quinoline-carbaldehyde with Phosphacumulene and Phosphaallene Ylides

“…Our continuing interest in the reactions of active phosphacumulene and phosphaallene (hexaphenylcarbodiphosphorane ylide) ylides to prepare carbocyclic and heterocyclic phosphorus compounds of biological interest, [26][27][28][29][30][31] led us to investigate and compare the behaviour of these phosphonium ylides with 4-aminoantipyrine (4-amino-1,5-dimethyl-2-phenyl-1,2dihydropyrazol-3-one-) (1), 4-amino-2-oxo-2H-chromene-3carbaldehyde (9), and 2-chloroquinoline-3-carbaldehyde (12) to synthesise new bioactive phosphorus compounds and their evaluation as antimicrobial agents.…”

Synthesis and spectroscopic characterization of some lanthanide(III) nitrate complexes of 3-[3-carboxyethyl-4,5- dimethylthiophene-2-yl)azo]pent-2,4-dione

“…17 The IR spectrum of HAAT adequately supported the conclusions made based on UV-Vis spectral data. 21 Apart from these vibrations, the infrared spectrum of the ligand also exhibited a strong band at 1678 cm -1 due to the ester carbonyl group. 2) exhibited a broad medium intensity band in the region 3300-3000 cm -1 and centred at 3100 cm -1 , which is assignable to the O-H stretching vibration of internally hydrogen bonded enolic group.…”

Novel pyrazole-3,4-dicarboxamides bearing biologically active sulfonamide moiety as potential carbonic anhydrase inhibitors

“…Pyrazole derivatives exhibit broad spectrum of biological activities such as analgesic, antiinflammatory, antipyretic, antibacterial, antifungal, and antiproliferative (Kuo et al, 1984;Bekhit et al, 2010;Schegol'kov et al, 2006;Tanitame et al, 2004;Li et al, 2006;Kostakis et al, 2002). Among them, some are used as phosphodiesterase inhibitors, COX-2 inhibitors, and CB1 cannabinoid receptors such as Sildenafil, Celecoxib and Rimonabant, respectively (Terrett et al, 1996;Dale et al, 2000;Penning et al, 1997;Lan et al, 1999;Francisco et al, 2002;Katoch-Rouse et al, 2003) (see Fig.…”